DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Applicant’s amendment submitted on 6/15/2026 is acknowledged. Claim 2 is canceled. Claims 15-16, 18-19, 22, and 24-27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/7/2025. Claims 1, 3-5, 7-11, and 13-14 are under examination on the merits.
Terminal Disclaimer
The terminal disclaimer filed on 6/15/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of Application No. 17/284,408 (recently issued as U.S. Patent No. 12709760 B1) has been reviewed and is accepted. The terminal disclaimer has been recorded.
Withdrawn Objections
The previous objections are hereby withdrawn, due to Applicant’s amendment submitted on 6/15/2026:
Specification: for minor informalities.
Response to Arguments
The previous rejections under 35 U.S.C. §103 are withdrawn because the cited references fail to teach the claims’ required VMD2 promoter consisting of a polynucleotide having at least 90% sequence identity to SEQ ID NO: 24, therefore, the arguments are moot.
Withdrawn Rejections
The previous rejections are hereby withdrawn, due to Applicant’s amendment submitted on 6/15/2026:
35 U.S.C. §103: Claims 1, 3, 7, 10-11, & 13-14 under 35 U.S.C. 103 as being unpatentable over Kirn et al. (PGPub US 20190255192 A1, filed 11/9/2018, published 8/22/2019; hereinafter referred to as “Kirn”) in further view of Miller et al. (PGPub US 20100273256 A1, filed 4/8/2009, published 10/28/2010; hereinafter referred to as “Miller”), Nenoi et al. (PGPub US 20080019946 A1, filed 4/19/2007, published 1/24/2008; hereinafter referred to as “Nenoi”) and Mallet et al. (PGPub US 20060051331 A1, filed 4/29/2003, published 3/9/2006; hereinafter referred to as “Mallet”); Claim 2 under 35 U.S.C. 103 as being unpatentable over Kirn, Miller, Nenoi, and Mallet (supra) as applied to claims 1, 3, 7, 10-11, & 13-14 above, and further in view of Petrukhin et al. PGPub US 20060105364 A1, filed 9/27/2005, published 5/18/2006; hereinafter referred to as “Petrukhin”); Claim 4 under 35 U.S.C. 103 as being unpatentable over Kirn, Miller, Nenoi, and Mallet (supra) as applied to claims 1, 3, 7, 10-11, & 13-14 above, and further in view of Wang, et al. (Gene Therapy 1999, 6: 667-675 doi: 10.1038/sj.gt.3300856. PMID: 10476227; hereinafter referred to as “Wang”) as evidenced by GenBank accession: MG550105.1 (1/10/2018); Claim 8 under 35 U.S.C. 103 as being unpatentable over Kirn, Miller, Nenoi, and Mallet (supra) as applied to claims 1, 3, 7, 10-11, & 13-14 above, and further in view of Miller et al. (J Virol. 2005 Sep;79(17):11434-42. doi: 10.1128/JVI.79.17.11434-11442.2005. PMID: 16103194; hereinafter referred to as “Miller II”); Claim 5 under 35 U.S.C. 103 as being unpatentable over Kirn, Miller, Nenoi, Mallet, and Petrukhin (supra) as applied to claim 2 above, and further in view of Wang, et al. (supra) as evidenced by GenBank accession: MG550105.1 (1/10/2018); Claim 9 under 35 U.S.C. 103 as being unpatentable over Kirn, Miller, Nenoi, Mallet, and Petrukhin and Wang as evidenced by GenBank accession: MG550105.1 (supra) as applied to claim 5 above, and further in view of GenBank accession: MK801287.1 (5/18/2019).
Double patenting: 1-5, 7-11 and 13-14 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 9-11, 13, 15-16, and 18-19 of copending Application No. 17/284,408 in view of Kirn, Miller, Nenoi, Mallet, Petrukhin, Miller II, Wang, as evidenced by GenBank accession: MG550105.1, and GenBank accession: MK801287.1 (supra).
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Scope of Enablement
Claims 1, 3-5, 7-11, and 13-14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for an AAV gene therapy vector comprising an RPE specific promoter consisting of all residues tested and shown to function as a promoter, does not reasonably provide enablement for similar AAV gene therapy vectors comprising an RPE specific promoter that consists of SEQ ID NO: 24. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The breadth of the claims is found in claim 1.
The nature of the invention is an adeno-associated viral (AAV) gene therapy vector comprising: a 5’ inverted terminal repeat (ITR) comprising SEQ ID NO: 23, a retinal pigment epithelium (RPE) specific promoter, wherein the RPE specific promoter is a VMD2 promoter consisting of a polynucleotide having at least 90% identity to SEQ ID NO: 24, a polynucleotide that encodes a Kir7.1 protein and has at least 90% sequence identity to SEQ ID NO: 25, a post transcriptional regulatory element (PRE), a polyadenylation signal, and a 3’ ITR of SEQ ID NO: 28 (claim 1).
The level of skill of one skilled in this art is high.
The specification teaches an AAV vector for targeting and expression in both iPSC-RPE cells and in vivo, and the vector, AAV27M8, encodes EGFP and Kir7.1 (Example 3; Table 1). Table 1 indicates that the vector has a 5’ UTR at nucleotide positions 1-141, a VMD2 promoter identical to SEQ ID NO: 24 at positions 169-1144 (as SEQ ID NO: 24 aligns at SEQ ID NO: 21 at these positions), a kozak sequence at positions 1169-1174, and the EGFP ORF at positions 1175-2983, and additional 3’ elements (Table 1). Notably, Table 1 fails to indicate what resides at positions 142-168 (the segment 5’ of the VMD2 promoter), or at positions 1145-1168 (the segment 3’ of the VMD2 promoter). These teachings do not enable the full breadth of the claims because it is not clear from the disclosure that SEQ ID NO: 24 is a functional promoter on its own, without these intervening sequences (positions 142-168 and 1145-1168) of the AAV27M8 vector.
It is noted that the prior art is silent to a promoter consisting of instant SEQ ID NO. 24. Therefore, all enablement thereof must come from the instant disclosure.
The state of the prior art is such that it is well established in the art that truncating a promoter has deleterious effects on expression (Fujimoto, et al. Nucleic Acids Res. 2000 Jul 1;28(13):2557-62. doi: 10.1093/nar/28.13.2557. PMID: 10871406). Fujimoto discloses that 5’ deletion of the proximal 181 bp region of the human telomerase catalytic subunit (hTERT) gene promoter resulted in a stepwise reduction in transcriptional activity, indicating that the proximal 181 bp region functions as a minimal core promoter (Fig. 1; p. 2559).
Thus, the state of the art recognized that it would be highly unpredictable that an incomplete (i.e., truncated) promoter would maintain transcriptional activity. In this case, the flanking sequences around SEQ ID NO: 24 in AAV27M8 could be required for promoter activity but are not required by the instant claims. One of skill in the art would neither expect nor predict the appropriate functioning of the AAV vectors or VMD2 promoter thereof as currently claimed.
In view of the lack of the predictability of the art to which the invention pertains as evidenced by Fujimoto, the lack of guidance and direction provided by applicants, and the absence of clear working examples that show SEQ ID NO: 24 alone is a functional promoter, undue experimentation would be required to make and use AAV vectors with a VMD2 promoter consisting of SEQ ID NO: 24 with a reasonable expectation of success, absent a specific and detailed description in applicant’s specification of how to effectively practice this and absent working examples providing evidence which is reasonably predictive that the claimed AAVs (and VMD2 promoter thereof) are functional, commensurate in scope with the claimed invention.
Moreover, claims not containing elements critical or essential to the practice of the invention, such as complete and/or verified functional VMD2 promoter sequences, are not enabled by the disclosure. See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEFFREY MARK SIFFORD whose telephone number is (571)272-7289. The examiner can normally be reached 8:30 a.m. - 5:30 p.m. ET with alternating Fridays off.
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/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
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